HbF Levels in Sickle Cell Disease Are Associated with Proportion of Circulating Hematopoietic Stem and Progenitor Cells and CC-Chemokines
The concentration of circulating hematopoietic stem and progenitor cells has not been studied longitudinally. Here, we report that the proportions of Lin-CD34+38- hematopoietic multipotent cells (HMCs) and of Lin-CD34+CD38+ hematopoietic progenitors cells (HPCs) are highly variable between individuals but stable over long periods of time, in both healthy individuals and sickle cell disease (SCD) patients. This suggests that these proportions are regulated by genetic polymorphisms or by epigenetic mechanisms. We also report that in SCD patients treated with hydroxyurea, the proportions of circulating HMCs and HPCs show a strong positive and negative correlation with fetal hemoglobin (HbF) levels, respectively. Titration of 65 cytokines revealed that the plasma concentration of chemokines CCL2, CCL11, CCL17, CCL24, CCL27, and PDGF-BB were highly correlated with the proportion of HMCs and HPCs and that a subset of these cytokines were also correlated with HbF levels. A linear model based on four of these chemokines could explain 80% of the variability in the proportion of circulating HMCs between individuals. The proportion of circulating HMCs and HPCs and the concentration of these chemokines might therefore become useful biomarkers for HbF response to HU in SCD patients. Such markers might become increasingly clinically relevant, as alternative treatment modalities for SCD are becoming available.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Cells - 9(2020), 10 vom: 29. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Minniti, Caterina P [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.03.2021 Date Revised 14.05.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/cells9102199 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315738111 |
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| 100 | 1 | |a Minniti, Caterina P |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HbF Levels in Sickle Cell Disease Are Associated with Proportion of Circulating Hematopoietic Stem and Progenitor Cells and CC-Chemokines |
| 264 | 1 | |c 2020 | |
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| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 19.03.2021 | ||
| 500 | |a Date Revised 14.05.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The concentration of circulating hematopoietic stem and progenitor cells has not been studied longitudinally. Here, we report that the proportions of Lin-CD34+38- hematopoietic multipotent cells (HMCs) and of Lin-CD34+CD38+ hematopoietic progenitors cells (HPCs) are highly variable between individuals but stable over long periods of time, in both healthy individuals and sickle cell disease (SCD) patients. This suggests that these proportions are regulated by genetic polymorphisms or by epigenetic mechanisms. We also report that in SCD patients treated with hydroxyurea, the proportions of circulating HMCs and HPCs show a strong positive and negative correlation with fetal hemoglobin (HbF) levels, respectively. Titration of 65 cytokines revealed that the plasma concentration of chemokines CCL2, CCL11, CCL17, CCL24, CCL27, and PDGF-BB were highly correlated with the proportion of HMCs and HPCs and that a subset of these cytokines were also correlated with HbF levels. A linear model based on four of these chemokines could explain 80% of the variability in the proportion of circulating HMCs between individuals. The proportion of circulating HMCs and HPCs and the concentration of these chemokines might therefore become useful biomarkers for HbF response to HU in SCD patients. Such markers might become increasingly clinically relevant, as alternative treatment modalities for SCD are becoming available | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a chemokine | |
| 650 | 4 | |a fetal hemoglobin | |
| 650 | 4 | |a hematopoietic stem and progenitor | |
| 650 | 4 | |a sickle cell disease | |
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| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a CCL11 protein, human |2 NLM | |
| 650 | 7 | |a CCL17 protein, human |2 NLM | |
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| 700 | 1 | |a Tolu, Seda S |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Zi |e verfasserin |4 aut | |
| 700 | 1 | |a Robert, Karl |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shouping |e verfasserin |4 aut | |
| 700 | 1 | |a Crouch, Andrew S |e verfasserin |4 aut | |
| 700 | 1 | |a Uehlinger, Joan |e verfasserin |4 aut | |
| 700 | 1 | |a Manwani, Deepa |e verfasserin |4 aut | |
| 700 | 1 | |a Bouhassira, Eric E |e verfasserin |4 aut | |
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